The Neural Basis of Functional MRI Responses

认知神经生理学和成像单元（UCNI）在结合电生理学和功能磁共振成像技术方面的目标是双重的。 首先，我们的目标是了解大脑中的电过程和血液动力学过程之间的关系，因为这种理解将直接影响使用fMRI在研究和临床应用中的无数研究。 第二，我们有兴趣研究如何从电极测量的活动在大脑中的一个点与活动在遥远的部分的大脑，如功能磁共振成像测量，因为这将提供洞察如何全球变化的皮层活动有助于响应的变化通常观察到在感觉处理。 在最简单的刺激条件下，电生理和fMRI反应是很好的协议。 例如，视觉刺激的呈现会引起视觉皮层中两种类型信号的突然积极反应，并且这两种信号被认为是高度相关的。 然而，当调查认知变量时，这种一致性可能会破裂，例如注意力的方向或感知可见性。 例如，在以前的工作中，我们证明了在知觉抑制期间，刺激是物理存在的，但在知觉上是不可见的，只有fMRI信号反映了初级视觉皮层中的知觉状态。 同一区域的神经元继续对刺激放电，而不管它是否被感知到。 这种差异被一些人认为是一个令人担忧的迹象，表明功能磁共振成像反应不能准确反映神经活动。 另一种观点可能是，这两种类型的信号提供了一个不同的，非冗余的大脑功能窗口。 在对差异进行任何解释之后，很明显，如果要将两种类型的测量整合到对大脑功能的连贯理解中，那么理解两种信号之间的关系是至关重要的。 本着这种精神，我们的大部分工作都是与邻近的神经生理学成像设施（NIF）密切合作的，在那里，训练有素的猴子在观看各种视觉刺激的同时进行常规扫描。 NIF的所有功能，包括同步神经生理学记录，微输注和磁铁中的电微刺激，提供了一系列独特的工具来研究与感觉和感知相关的大脑生理学。 我们目前正在使用多种方法来了解大脑中神经和功能磁共振成像信号之间的关系。 第一种方法将功能性MRI成像与神经组织的摘除或失活相结合。 在一个项目中，我们损伤了初级视觉皮层，这是视觉信息到达视觉皮层的瓶颈，并使用功能磁共振成像来询问大脑的其他部分是否仍然会对视觉刺激做出反应。 我们发现，V1区以外区域的功能磁共振成像反应令人惊讶地完好无损，即使主要的神经高速公路不再可用。 这一发现表明视觉系统中存在替代途径，绕过初级视觉皮层到达联合皮层。 目前，实验室的研究正在调查在关联区域观察到的fMRI活动是否反映了正常的神经活动（动作电位的尖峰），或者那里的神经反应是否是沉默的，因此与fMRI信号不同。 有趣的是，当在相同的动物中另外灭活丘脑的膝状体核时，残留的活性被完全消除。 这些多阶段的实验，涉及病变，药理学失活，电生理学和功能成像在同一动物，提供了新的见解在大脑中的视觉通路，除了他们提供的信息，关于神经和功能磁共振成像信号之间的关系。 我们也开始将联合收割机在磁孔内的电微刺激与清醒猴子的功能成像结合起来。 这种技术最近被用来推断区域之间的结构和功能连接，远离刺激部位的功能激活表明这种连接。 我们刺激上级丘的初步结果显示，纹状和纹外视皮层被激活。 最后，我们使用植入的多触点电极，在功能磁共振成像扫描过程中直接对大脑活动进行了大量记录。 为了实现这一目标，我们引导了两种不同类型的MR兼容的可植入电极的开发：多触点线性阵列和皮层脑电图电极。 这些特殊的电极由特殊金属制成，在功能扫描期间产生最小的伪影。 在几个皮层区域植入这些阵列后，我们监测了功能磁共振成像和猴子大脑神经信号之间活动的协变，这些猴子在扫描仪中处于警觉和清醒状态。 我们发现，大脑表面某个点的自发电活动与整个皮层的功能磁共振成像反应之间存在广泛的相关性。 这种相关性的基础现在才开始被理解，并且被认为是在静息状态下大脑的普遍，连贯和全局波动。 这一发现对许多研究正常和患者群体静息状态功能连接的研究人员具有潜在的重要意义。 具体地说，传统上已经将全局皮层信号作为与神经活动无关的伪影移除。 我们的研究结果表明，这一结论是错误的，并且全局信号可能对于理解静息态大脑生理学至关重要。 大脑皮层中大规模信号波动的实际意义，包括其对感觉处理的影响，是目前我们研究的重点。

The goals of the Unit on Cognitive Neurophysiology and Imaging (UCNI) in combining electrophysiology and fMRI techniques are two-fold. First, we aim to understand the relationship between the electrical and hemodynamic processes in the brain, since this understanding will directly impact the myriad studies using fMRI in research and clinical applications. Second, we are interested to study how activity measured from an electrode at one point in the brain covaries with activity in distant parts of the brain, as measured with fMRI, as this will provide insight into how global changes in cortical activity contribute to the response variability commonly observed during sensory processing. Under most simple stimulus conditions, electrophysiological and fMRI responses are in good agreement. For example, the presentation of a visual stimulus will elicit abrupt positive responses of both types of signals in the visual cortex, and the two signals are seen to be highly correlated. However, this agreement can break down when investigating cognitive variables, such as the direction of attention or the perceptual visibility. In previous work, for example, we demonstrated that during perceptual suppression, where a stimulus is physically present but perceptually invisible, only the fMRI signal reflected the perceptual state in the primary visual cortex. Neurons in the same area continued to fire electrical discharges to the stimulus regardless of whether or not it was perceived. This sort of discrepancy has been taken by some as an alarming sign that fMRI responses do not accurately reflect neural activity. Another viewpoint may be that the two types of signals offer a different, non-redundant, window on brain function. Following either interpretation of the discrepancy, it is clear that understanding the relationship between the two signals is of utmost importance if the two types of measurements are to be integrated into a coherent understanding of brain function. In this spirit, much of our work is in close collaboration with the neighboring Neurophysiology Imaging Facility (NIF), where trained monkeys are scanned routinely while viewing a variety of visual stimuli. The repertoire of the NIF, including simultaneous neurophysiological recordings, microinfusion, and electrical microstimulation in the magnet, offers a range of unique tools to study brain physiology related to sensation and perception. We are presently using multiple approaches to understand the relationship between neural and fMRI signals in the brain. The first approach combines functional MRI imaging with the extirpation or inactivation of neural tissue. In one project, we lesioned the primary visual cortex, which is the bottleneck of visual information reaching the visual cortex, and used fMRI to ask whether other parts of the brain would still respond to visual stimuli. We found that fMRI responses in areas beyond V1 were surprisingly intact, even though the main neural highway was no longer available. This finding suggested alternative pathways in the visual system, circumventing the primary visual cortex to reach association cortex. Present research in the lab is investigating whether the fMRI activity observed in the association areas reflects normal neural activity (the spiking of action potentials), or whether neural responses there are silent, and therefore different from the fMRI signal. Interestingly, the residual activity was completely abolished when the geniculate nucleus of the thalamus was additionally inactivated in the same animals. These multi-stage experiments, involving lesions, pharmacological inactivation, electrophysiology, and functional imaging in the same animals, are providing new insights into visual pathways in the brain, in addition to the information they offer regarding the relationship between neural and fMRI signals. We have also begun to combine electrical microstimulation inside the magnetic bore with functional imaging in awake monkeys. This technique has recently been used to infer structural and functional connectivity between areas, with functional activation far away from the site of stimulation indicating such a connection. Our preliminary results stimulating the superior colliculus have shown activation in the striate and extrastriate visual cortex. Finally, we have done extensive recordings of brain activity directly during fMRI scanning using implanted multicontact electrodes. In order to accomplish this, we steered the development of MR-compatible, implantable electrodes of two different sorts: multicontact linear arrays, and electrocorticogram electrodes. These special electrodes were constructed with special metals that produce minimal artifacts during functional scans. Following implantation of these arrays in several cortical areas, we monitored the covariation in activity between fMRI and neural signals in the brain of monkeys that were sitting alert and awake in the scanner. We found there to be a widespread correlation between the spontaneous electrical activity at a point on the brains surface and the fMRI responses throughout wide swathes of the cortex. The basis of this correlation is only now beginning to be understood, and is thought to arise from a general, coherent and global fluctuation over the brain in the resting state. This finding has potentially important implications for many researchers studying resting state functional connectivity in normal and patient populations. Specifically, the global cortical signal has traditionally been removed as an aritifact irrelevant to neural activity. Our findings suggest that this conclusion is erroneous, and that the global signal may be critical for understanding resting state brain physiology. The practical implications of large-scale signal fluctuations in the cortex, including its impact on sensory processing, is presently at the focus of our research.